Effects of cisapride on QT interval in infants: A prospective study

Guala, Andrea; Pastore, Guido; Licardi, G; Noé, G P; Zolezzi, F

doi:10.1067/mpd.2000.106306

Cited by 9 publications

(3 citation statements)

References 10 publications

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“…Several proarrhythmia risk factors have been identified: overdose or concomitant use of drugs that are metabolized through the P-450 cytochrome or prolong the Q-T interval, heart disease, electrolyte disturbances, prematurity, and newborn age [15,17]. From a review of the effects of cisapride on the QTc interval, it appears that preterm and term infants younger than 3 months of age are particularly sensitive to the cardiac effects of cisapride (table 6).…”

Section: Discussionmentioning

confidence: 99%

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

Zamora¹,

Belli²,

Friedli

et al. 2004

Neonatology

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We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28–36 weeks) were studied at a median chronological age of 29 (range 3–132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 ± 7 vs. 433 ± 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 ± 5 vs. 78 ± 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 ± 0.2 s vs. 1.05 ± 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.

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Section: Discussionmentioning

confidence: 99%

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

Zamora¹,

Belli²,

Friedli

et al. 2004

Neonatology

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“…Previous investigators also showed that very low concentrations of cisapride could prolong action potential in rabbit Purkinje fibers [32]. However, several recent studies showed that the QTc interval was not prolonged [14,18,23], or was even shortened in patients taking cisapride [13,34]. In a recent study by Rahme et al [33] in pigs, there was no significant effect of cisapride infusion (0.1 mg/kg) on the QTc (with a baseline = of 500 ms; after cisapride, it was = 486 ms) or the effective refractory periods of the left and right ventricles.…”

Section: Comparisons To Previous Studiesmentioning

confidence: 99%

“…Furthermore, two papers described shortening of the QTc interval by cisapride in pediatric patients [13,34]. Although a genetic predisposition might explain the discrepancy among different studies [4], it is possible that cisapride exerts other electrophysiological effects.…”

mentioning

confidence: 99%

Inhibition of L-Type Ca<sup>2+</sup> Current in Guinea Pig Ventricular Myocytes by Cisapride

Chiang¹,

Wang²,

Luk³

2004

J Biomed Sci

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The effect of cisapride on L-type Ca²⁺ current (I_Ca,L) was studied in guinea pig ventricular myocytes using a whole-cell voltage-clamp technique and a conventional action potential recording method. Myocytes were held at –40 mV, and internally dialyzed and externally perfused with Na⁺- and K⁺-free solutions; cisapride elicited a concentration-dependent block of peak I_Ca,L, with a half-maximum inhibition concentration (IC₅₀) of 46.9 µM. There was no shift in the reversal potential, nor any change in the shape of the current-voltage relationship of I_Ca,L in the presence of cisapride. Inhibition of cisapride was not associated with its binding to serotonin or to α-adrenergic receptors because ketanserin, SB203186, and prazosin had no effect on the inhibitory action of cisapride on I_Ca,L. Cisapride elicited a tonic block and a use-dependent block of I_Ca,L.These blocking effects were voltage dependent as the degree of inhibition at –40 mV was greater than that at –70 mV. Cisapride shifted the steady-state inactivation curve of I_Ca,L in the negative direction, but had no effect on the steady-state activation curve. Cisapride also delayed the kinetics of recovery of I_Ca,L from inactivation. At a slow stimulation frequency (0.1 Hz), the action potential duration in guinea pig papillary muscles showed biphasic effects; it was prolonged by lower concentrations of cisapride, but shortened by higher concentrations. These findings suggest that cisapride preferentially binds to the inactivated state of L-type Ca²⁺ channels. The inhibitory effect of cisapride on I_Ca,L might play an important role in its cardiotoxicity under pathophysiological conditions, such as myocardial ischemia.

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Current Awareness

2000

Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Effects of cisapride on QT interval in infants: A prospective study

Cited by 9 publications

References 10 publications

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

Inhibition of L-Type Ca<sup>2+</sup> Current in Guinea Pig Ventricular Myocytes by Cisapride

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Effects of cisapride on QT interval in infants: A prospective study

Cited by 9 publications

References 10 publications

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

Inhibition of L-Type Ca<sup>2&plus;</sup> Current in Guinea Pig Ventricular Myocytes by Cisapride

Current Awareness

Contact Info

Product

Resources

About

Inhibition of L-Type Ca<sup>2+</sup> Current in Guinea Pig Ventricular Myocytes by Cisapride